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Patient-derived endothelial progenitor cells improve vascular graft patency in a rodent model

机译:在啮齿动物模型中,患者来源的内皮祖细胞可改善血管移植的通畅性

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Late outgrowth endothelial progenitor cells (EPCs) derived from the peripheral blood of patients with significant coronary artery disease were sodded into the lumens of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts. Grafts (1 mm inner diameter) were denucleated and sodded either with native EPCs or with EPCs transfected with an adenoviral vector containing the gene for human thrombomodulin (EPC + AdTM). EPC + AdTM was shown to increase the in vitro rate of graft activated protein C (APC) production 4-fold over grafts sodded with untransfected EPCs (p < 0.05). Unsodded control and EPC-sodded and EPC + AdTM-sodded grafts were implanted bilaterally into the femoral arteries of athymic rats for 7 or 28 days. Unsodded control grafts, both with and without denucleation treatment, each exhibited 7 day patency rates of 25%. Unsodded grafts showed extensive thrombosis and were not tested for patency over 28 days. In contrast, grafts sodded with untransfected EPCs or EPC + AdTM both had 7 day patency rates of 88-89% and 28 day patency rates of 75-88%. Intimal hyperplasia was observed near both the proximal and distal anastomoses in all sodded graft conditions but did not appear to be the primary occlusive failure event. This in vivo study suggests autologous EPCs derived from the peripheral blood of patients with coronary artery disease may improve the performance of synthetic vascular grafts, although no differences were observed between untransfected EPCs and TM transfected EPCs.
机译:来自患有严重冠状动脉疾病的患者外周血的晚期生长内皮祖细胞(EPC)被浸入小直径扩张的聚四氟乙烯(ePTFE)血管移植物的腔中。将移植物(内径1毫米)去核并用天然EPC或用含有人血栓调节蛋白基因(EPC + AdTM)的腺病毒载体转染的EPC浸种。与未转染的EPC浸泡的移植物相比,EPC + AdTM可以使移植物活化蛋白C(APC)的体外产生速率提高4倍(p <0.05)。将未加标本的对照和EPC贴标以及EPC + AdTM贴标的移植物双侧植入无胸腺大鼠的股动脉内7或28天。不论是否进行去核处理,未接种的对照移植物均显示25%的7天通畅率。未固定的移植物表现出广泛的血栓形成,并且在28天内未进行通畅性测试。相反,未转染的EPC或EPC + AdTM浸透的移植物的7天通畅率分别为88-89%和28天通畅率分别为75-88%。在所有浸泡的移植条件下,在近端和远端吻合处均观察到内膜增生,但这似乎不是主要的闭塞性失败事件。这项体内研究表明,尽管未转染的EPC和TM转染的EPC之间未观察到差异,但源自冠心病患者外周血的自体EPC可能会改善合成血管移植物的性能。

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